| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First line chemotherapy at patients with metastatic breast cancer |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the Progression Free Survival (PFS) in patients with metastatic breast cancer after treatment with taxane plus bevacizumab with (TXB) or without capecitabine (TB). |
|
| E.2.2 | Secondary objectives of the trial |
• To determine the objective response rate in both arms.
• To determine the duration of response in both arms.
• To determine the Time to Progression (TTP) in both arms.
• To determine the clinical benefit defined as CR, PR, or stable disease ≥ 24 weeks in both arms.
• To determine the overall survival rate 3 years after “Last Patient In”.
• To determine PFS and TTP response rates in patient’s ≥ age 65.
• To determine the toxicity and compliance in both arms.
• To determine the predictive value of serum markers such as VEGF.
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age ≥18 years.
2. Female and Male patients.
3. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
4. Complete baseline documentation sent to GBG Forschungs GmbH.
5. ECOG performance status 0-2.
6. Histological confirmed carcinoma of the breast with no over expression of HER2.
7. Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.
8. Patients must have either measurable or non-measurable target lesions according to RECIST criteria (phase III). Complete staging work-up within 4 weeks prior to registration. All patients must have chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated.
9. The following previous systemic treatment are eligible:
• (neo)adjuvant chemotherapy. However if (neo)adjuvant chemotherapy was anthracycline based, the maximum cumulative dose of prior anthracycline therapy must not exceed 360 mg/m2 for doxorubicin and 720 mg/m2 for epirubicin. If taxanes or capecitabine were part of (neo)adjuvant treatment, a treatment-free interval of > 6 months is requested.
• adjuvant endocrine therapy.
• palliative endocrine treatments.
• treatment with bisphosphonates.
• treatment with immunotherapies.
10. Patients have to be fully recovered from previous radiotherapy. At least one measurable lesion must be completely outside the radiation field or there must be pathologic proof of progressive disease.
11. Absolute neutrophil count 2000 cells/l, platelet count 100,000 cells/l.
12. Bilirubin 1,5 x the upper limit of normal for the institution (ULN); elevation of transaminases and alkaline phosphatase <2.5 x ULN or < 5 x ULN for patients with liver metastases.
13. Creatinine 1,25 x ULN or creatinin-clearance ≥ 50 ml/min (according to Cockcroft Gault). Urine dipstick for proteinuria <2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours.
14. Negative pregnancy test (urine or serum) within 14 days prior to registration for all women of childbearing potential.
15. Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating site.
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| E.4 | Principal exclusion criteria |
1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
2. Previous chemotherapy for metastatic disease, concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or replacement therapy). Bisphosphonates may be continued.
3. Life expectancy of less than 3 months.
4. Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including AIDS and serious active infection).
5. Known or suspected congestive heart failure (> NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP > 150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
6. Currently active infection.
7. Active peptic ulcer, incomplete wound healing or unhealed bone fracture.
8. Previous thromboembolic events, known hemorrhagic diathesis, coagulopathy with increased bleeding risk, or treatment with anticoagulants. Current or recent (within 10 days of first dose of bevacizumab) use of acetylic acid (> 325mg/day) or clopidogrel (> 75mg/day).
9. Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel, ulcerative colitis; abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
10. Major surgery within the last 28 days or anticipation of the need for major surgery during study treatment with bevacizumab. No minor surgeries including insertion of an indwelling catheter within 24 h prior to randomization.
11. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy with complete resolution of symptoms and discontinuation of all steroids.
12. History of other malignancy within the last 5 years which could affect the diagnosis or assessment or outcome of metastatic breast cancer.
13. Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational drug within 30 days prior to study entry.
14. Treatment with sorivudine or derivates e.g. brivudin.
15. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intra uterine contraceptive devices, sterilization) during study treatment.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 40 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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